33 research outputs found

    Structural basis for tropomyosin overlap in thin (actin) filaments and the generation of a molecular swivel by troponin-T

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    Head-to-tail polymerization of tropomyosin is crucial for its actin binding, function in actin filament assembly, and the regulation of actin-myosin contraction. Here, we describe the 2.1 Å resolution structure of crystals containing overlapping tropomyosin N and C termini (TM-N and TM-C) and the 2.9 Å resolution structure of crystals containing TM-N and TM-C together with a fragment of troponin-T (TnT). At each junction, the N-terminal helices of TM-N were splayed, with only one of them packing against TM-C. In the C-terminal region of TM-C, a crucial water in the coiled-coil core broke the local 2-fold symmetry and helps generate a kink on one helix. In the presence of a TnT fragment, the asymmetry in TM-C facilitates formation of a 4-helix bundle containing two TM-C chains and one chain each of TM-N and TnT. Mutating the residues that generate the asymmetry in TM-C caused a marked decrease in the affinity of troponin for actin-tropomyosin filaments. The highly conserved region of TnT, in which most cardiomyopathy mutations reside, is crucial for interacting with tropomyosin. The structure of the ternary complex also explains why the skeletal- and cardiac-muscle specific C-terminal region is required to bind TnT and why tropomyosin homodimers bind only a single TnT. On actin filaments, the head-to-tail junction can function as a molecular swivel to accommodate irregularities in the coiled-coil path between successive tropomyosins enabling each to interact equivalently with the actin helix

    Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study

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    Aims: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy.Methods: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates.Results: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992–2008 or 1993–2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries.Conclusions: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque

    食道癌術後肺合併症の検討 : とくに迷走神経と肺合併症との関連 第2編 実験的検討

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    食道癌術後肺合併症の検討 : とくに迷走神経と肺合併症との関連 第1編 臨床的検討

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    Fuzzy Morphology with Fuzzy Adaptive Structuring Element and Its Application to Seal Defect Testing

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    乳管造影にて異常所見のえられた微小非浸潤性乳管癌の2症例

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    An enlarged intramuscular venous malformation in the femoral region successfully treated with complete resection

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    Introduction: Intramuscular venous malformations have been previously described as intramuscular hemangiomas, and various therapies have been applied for their treatment. This condition is relatively rare, and therefore, physicians often struggle to determine the appropriate therapy. We presented a case of an enlarged intramuscular venous malformation relapsed after surgery successfully treated with complete resection. Presentation of case: We presented a case of an enlarged intramuscular venous malformation with postoperative recurrence successfully treated with complete resection. A 63-year-old woman presented with a subcutaneous mass in the right distal thigh. She experienced swelling in the right thigh 19 years previously and was diagnosed with a venous aneurysm. Three-dimensional CT angiography confirmed the presence of an irregular vessel assumed to be the feeding vessel, which was dendritically branched from the deep femoral artery. We performed surgical complete resection. Her pain and gait disturbance improved after surgery, and she has not experienced recurrence of the mass for the past 2 years. Discussion: Conservative therapy is initially used for venous malformations. Sclerotherapy, laser therapy, or surgical resection is considered after low-dose aspirin therapy, in combination with the use of compressive garments. Surgical resection is indicated for completely resectable lesions and is appropriate for large lesions in terms of cosmetic benefit. However, partial resection may result in excessive bleeding or postoperative recurrence. Conclusion: The therapy for venous malformations should be decided based on the degree of disability in daily living, adjacent tissue damage, and cosmetic concerns after appropriate differential diagnostic investigations and biopsy
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